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Karyopherins regulate nuclear pore complex barrier and transport function
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2017
- Publisher :
- Rockefeller University Press, 2017.
-
Abstract
- Kapinos et al. show that nuclear pore complex permeability and cargo release functionalities are concomitantly regulated by karyopherin occupancy and turnover in a systematic continuum. This highlights increasingly important roles for the soluble nucleocytoplasmic transport machinery that depart from established views of the nuclear pore complex selectivity mechanism.<br />Nucleocytoplasmic transport is sustained by karyopherins (Kaps) and a Ran guanosine triphosphate (RanGTP) gradient that imports nuclear localization signal (NLS)–specific cargoes (NLS-cargoes) into the nucleus. However, how nuclear pore complex (NPC) barrier selectivity, Kap traffic, and NLS-cargo release are systematically linked and simultaneously regulated remains incoherent. In this study, we show that Kapα facilitates Kapβ1 turnover and occupancy at the NPC in a RanGTP-dependent manner that is directly coupled to NLS-cargo release and NPC barrier function. This is underpinned by the binding affinity of Kapβ1 to phenylalanine–glycine nucleoporins (FG Nups), which is comparable with RanGTP·Kapβ1, but stronger for Kapα·Kapβ1. On this basis, RanGTP is ineffective at releasing standalone Kapβ1 from NPCs. Depleting Kapα·Kapβ1 by RanGTP further abrogates NPC barrier function, whereas adding back Kapβ1 rescues it while Kapβ1 turnover softens it. Therefore, the FG Nups are necessary but insufficient for NPC barrier function. We conclude that Kaps constitute integral constituents of the NPC whose barrier, transport, and cargo release functionalities establish a continuum under a mechanism of Kap-centric control.
- Subjects :
- alpha Karyopherins
0301 basic medicine
Active Transport, Cell Nucleus
Guanosine triphosphate
Biology
environment and public health
Article
Xenopus laevis
03 medical and health sciences
chemistry.chemical_compound
otorhinolaryngologic diseases
Animals
Humans
Nuclear pore
Research Articles
Barrier function
Membrane Glycoproteins
Cell Biology
beta Karyopherins
Nuclear Pore Complex Proteins
Kinetics
stomatognathic diseases
ran GTP-Binding Protein
030104 developmental biology
chemistry
Nucleocytoplasmic Transport
Karyopherins
Ran
Nuclear Pore
Biophysics
Nucleoporin
Nuclear localization sequence
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 216
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....15a72074c4f7dea53da9c02809cfc16b
- Full Text :
- https://doi.org/10.1083/jcb.201702092